Drug Resistance in Epilepsy: The Role of the Blood–Brain Barrier

  1. Gregory Bock and
  2. Jamie A. Goode
  1. N. Joan Abbott1,
  2. Ehsan U. Khan1,
  3. Christopher M. S. Rollinson1,
  4. Andreas Reichel1,
  5. Damir Janigro2,
  6. Stephen M. Dombrowski2,
  7. Michael S. Dobbie1 and
  8. David J. Begley1

Published Online: 7 OCT 2008

DOI: 10.1002/0470846356.ch4

Mechanisms of Drug Resistance in Epilepsy: Novartis Foundation Symposium 243

Mechanisms of Drug Resistance in Epilepsy: Novartis Foundation Symposium 243

How to Cite

Abbott, N. J., Khan, E. U., Rollinson, C. M. S., Reichel, A., Janigro, D., Dombrowski, S. M., Dobbie, M. S. and Begley, D. J. (2002) Drug Resistance in Epilepsy: The Role of the Blood–Brain Barrier, in Mechanisms of Drug Resistance in Epilepsy: Novartis Foundation Symposium 243 (eds G. Bock and J. A. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470846356.ch4

Author Information

  1. 1

    Blood–Brain Barrier Research Group, Centre for Neuroscience Research, King's College London, London SE1 1UL, UK

  2. 2

    Cerebrovascular Research, Cleveland Clinic Foundation, Cleveland, Ohio OH 44195, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 25 MAR 2002

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470841464

Online ISBN: 9780470846353

SEARCH

Summary

The blood–brain barrier (BBB) is formed by the endothelial cells lining the brain microvessels. Complex tight junctions linking adjacent endothelial cells make brain capillaries around 100 times tighter than peripheral capillaries to small hydrophilic molecules. As a result, drugs required to act in the brain, including anti-epileptic drugs (AEDs), have generally been made lipophilic, and are thus able to cross the brain endothelium via the lipid membranes. However, such lipophilic drugs are potential substrates for efflux carriers of the BBB, particularly P glycoprotein (Pgp), predominantly located on the endothelial luminal membrane. It is estimated that up to 50% of drug candidates may be substrates for Pgp. The barrier phenotype of the brain endothelium is induced and maintained by chemical factors released by brain cells, particularly perivascular astrocytic end feet. In several neuropathological conditions, the BBB is disturbed, either as a result of pathology of the endothelium, or of the cells responsible for barrier induction and maintenance. During epileptic attacks, there may be transient BBB opening in the epileptogenic focus. There is evidence that under such pathological conditions, ‘second line defence’ mechanisms in perivascular glia may be up-regulated, including expression of Pgp and other drug efflux transporters. This complicates interpretation of drug resistance in epilepsy, and therapeutic strategies.